Nov 14, 2025 12:00:00

Viagra may be useful in treating congenital hearing loss caused by genetic mutations

Congenital hearing loss, a condition that affects

1.62 people per 1,000 , is a condition that requires treatment. New research has identified a genetic mutation that causes a rare form of congenital hearing loss and suggests that it may be treatable with common supplements or the erectile dysfunction drug Viagra (sildenafil) .

JCI - Carboxypeptidase D deficiency causes hearing loss amenable to treatment
https://www.jci.org/articles/view/192090

UChicago scientists discover gene mutation linked to deafness — and identify possible treatments | Biological Sciences Division | The University of Chicago
https://biologicalsciences.uchicago.edu/news/gene-mutation-linked-deafness

Viagra Reverses Damage Behind One Type of Deafness, Scientists Discover : ScienceAlert
https://www.sciencealert.com/viagra-reverses-damage-behind-one-type-of-deafness-scientists-discover

To investigate the genetic causes of congenital hearing loss, the research team studied three unrelated families from Turkey, all of whom had five members with a type of congenital hearing loss called sensorineural hearing loss.

When the researchers examined the genes of these people with congenital hearing loss, they found three different genetic mutations in the CPD gene, which encodes an enzyme called carboxypeptidase D (CPD) . Furthermore, the scientists analyzed extensive genetic databases and found that other people with CPD mutations also tend to develop hearing loss early.

Next, the team conducted studies in mice to better understand how the CPD gene affects hearing. Normally, the CPD gene encodes CPD, which produces the amino acid

arginine , which increases the production of nitric oxide , an important neurotransmitter that helps transmit signals through the nervous system.

Further analysis of the cochlea tissue of mice transfected with an inactive CPD gene, as well as human skin tissue and cells, revealed that the CPD gene mutation inhibits the production of arginine and also reduces the amount of a key compound called cyclic guanosine monophosphate (cGMP) .

Furthermore, the research team investigated the effects of CPD gene mutations in fruit flies and found that fruit flies with CPD gene mutations exhibited behavioral changes consistent with damage to the inner ear, such as hearing loss and balance disorders.

Without arginine, the mouse ears lack adequate levels of signaling molecules like nitric oxide and cGMP, which leads to oxidative stress and death of sensory cells, especially hair cells , which are essential for hearing.

'We found that CPD maintains arginine levels in hair cells and enables rapid signaling cascades by producing nitric oxide,' said Long Zhai , co-author of the paper and professor of neurology at the University of Chicago. 'Thus, these hair cells are particularly sensitive or vulnerable to loss of CPD, even though CPD is ubiquitously expressed in other cells throughout the nervous system.'

Finally, the research team tested approaches to treat the pathway disrupted by the CPD mutation. One was arginine supplements, which are lost in the CPD mutation, and the other was Viagra, which is known to stimulate the pathway affected by reduced nitric oxide. Both approaches improved hair cell survival and reduced behavioral changes caused by hearing loss in fruit flies.

'What makes this research truly impactful is that we not only uncover the cellular and molecular mechanisms underlying this type of hearing loss, but also identify a promising treatment for these patients,' said Zai. 'This is a great example of our efforts to repurpose FDA-approved drugs to treat rare diseases.'